Degeneration of cochlear neurons after amikacin intoxication in the rat

Abstract

Intoxication with high doses of the aminoglycoside antibiotic amikacin in a supranormal sensitive period in the rat induces complete destruction of the inner and outer hair cells in the organ of Corti in all turns, whereas the supporting cells remain partially preserved in the upper turns. With increasing survival time, the number of ganglion cells in the spiral ganglion decreases progressively, reaching a minimum of about 10% surviving cells after 12 months. Both type I and type II neurons are subject to retrograde degeneration, although type-II cells degenerate more slowly than type-I cells. The presence or absence of supporting cells in the organ of Corti does not seem to influence neuronal degeneration. This retrograde degeneration is similar in all animals so far studied but its time course is different from different species. Retrograde degeneration after destruction of Corti's organ is a long-lasting process and is never completed at once. This must be taken into consideration in the treatment of total deafness with electric stimulation of surviving neurons.

Ouabain Induces Apoptotic Cell Death in Type I Spiral Ganglion Neurons, but not Type II Neurons

“…Type II neurons have been shown to have some selective survival advantage over the type I neurons in cat after ototoxic lesions of the organ of Corti (Spoendlin 1975;Lim 1976;Bichler et al 1983;Leak and Hradek 1988), noise trauma (Spoendlin 1975;Lim 1976), or transection of the cochlear nerve (Spoendlin 1975). Some of these studies also reported the presence of a new type of neuron (type III) after various insults.…”

Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

“…In some models, extensive HC death in the adult rodent organ of Corti can lead to SC death and complete degeneration of the organ within weeks (Bichler et al 1983;Fredelius 1988;Fredelius et al 1988;Lenoir et al 1999). The underlying causes for the SC death are unknown.…”

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca2+]iwithin a Set Range

“…Studies of auditory system reveal that pre-and postsynaptic sources of neurotrophic support cooperate to prevent programmed cell death. Type I SGNs, which constitute Ͼ90% of the population, receive presynaptic input from the inner hair cells and are dependent on them for survival (Spoendlin, 1975;Webster and Webster, 1981;Koitchev et al, 1982;Bichler et al, 1983). As with other cells in the vicinity of the neuron and its terminals, presynaptic cells can contribute to neuronal survival by releasing neurotrophic factors.…”

“…Hair cells can be selectively killed in vivo with aminoglycoside antibiotics, thus deafferenting the SGNs. This results in the eventual death of the SGNs (Spoendlin, 1975;Webster and Webster, 1981;Koitchev et al, 1982;Bichler et al, 1983), even though the central projection remains intact. This suggests that different sources of neurotrophic stimuli are summed to a threshold to support survival.…”